EA 3647 Physiopathologie et diagnostic des infections microbiennes, Université Versailles St Quentin, and Laboratoire de Microbiologie, Hôpital Raymond Poincaré, AP-HP, Garches, France.
Cell Microbiol. 2011 May;13(5):692-704. doi: 10.1111/j.1462-5822.2010.01565.x. Epub 2011 Jan 5.
Changes in the cell envelope composition of mycobacteria cause major changes in cytokine profiles of infected antigen presenting cells. We describe here the modulation of inflammatory responses by Mycobacterium abscessus, an emerging pathogen in cystic fibrosis. M. abscessus is able to switch from a smooth (S) to a rough (R) morphotype by the loss of a surface glycopeptidolipid. R variants are associated with severe clinical forms and a 'hyper-proinflammatory' response in ex vivo and in vivo models. Using partitioning of cell surface components we found that a complex fraction, more abundant in R variants than in S variants, made a major contribution to the TLR-2-dependent hyper-proinflammatory response induced by R variants. Lipoproteins were the main TLR-2 agonists in this fraction, consistent with the larger amounts of 16 lipoproteins in cell surface extracts from R variants; 15 out of 16 being more strongly induced in R variant than in S variant. Genetic interruption of glycopeptidolipid pathway in wild-type S variant resulted in R phenotype with similar induction of lipoprotein genes. In conclusion, R morphotype in M. abscessus is associated with increased synthesis/exposure at the cell surface of lipoproteins, these changes profoundly modifying the innate immune response through TLR-2-dependent mechanisms.
分枝杆菌细胞包膜成分的变化会导致感染的抗原呈递细胞中细胞因子谱发生重大变化。我们在这里描述了分枝杆菌脓肿，一种囊性纤维化新兴病原体，对炎症反应的调节。分枝杆菌脓肿能够通过表面糖脂的缺失从光滑（S）形态转变为粗糙（R）形态。R 变体与严重的临床形式和体外和体内模型中的“超炎症反应”有关。使用细胞表面成分的分区，我们发现一个复杂的部分，在 R 变体中比在 S 变体中更丰富，对 R 变体诱导的 TLR-2 依赖性超炎症反应有很大贡献。脂蛋白是该部分中主要的 TLR-2 激动剂，与 R 变体细胞表面提取物中 16 种脂蛋白的含量较大一致；其中 15 种在 R 变体中比在 S 变体中诱导更强。在野生型 S 变体中中断糖脂途径的基因导致 R 表型，同时诱导脂蛋白基因的表达增加。总之，分枝杆菌脓肿中的 R 形态与脂蛋白在细胞表面的合成/暴露增加有关，这些变化通过 TLR-2 依赖的机制极大地改变了先天免疫反应。
